CN101815506B - Oral drug delivery device for active ingredients - Google Patents

Abstract

The invention relates to an oral delivery device (10) in the form of an elongated tubular body enabling the passage of liquid in and out (12, 14) at both ends, having a one-way valve (16) at one end and containing at least one matrix (18) consisting of at least one neutral support (20) and a coating (22) of a different colour to the neutral support and containing at least one active ingredient.

Description

Oral drug delivery device for active ingredients

technical field

The present invention relates to an oral drug delivery device, which can observe the ingestion of medicine.

Background technique

There are many problems with taking medicines in children and the elderly.

In fact, it is very difficult to ingest through traditional solid pharmaceutical dosage forms such as tablets and capsules.

In addition, although liquid preparations such as syrups and oral solutions are simple to use, there are also obvious technical defects.

First, many active ingredients cannot exist in liquid form for reasons of solubility, stability or taste. The stability of drugs in liquid form is difficult to control because degradation and hydrolysis of the drug are exacerbated by the presence of water.

Second, liquid pharmaceutical products generally require the use of antimicrobial preservatives that are difficult to control and cause unpleasant residual odors.

Furthermore, in order to ensure that the patient takes the proper dose of the drug, the volume of fluid delivered needs to be minimized. Usually, for adults, the volume of liquid is about 15ml, which is equivalent to a tablespoon, and for children, it is about 5ml, which is equivalent to a teaspoon. However, it is difficult to control the dissolved amount of the active ingredient and the taste of the preparation with such a small volume. A particularly illustrative example of this is the preparations containing ibuprofen or paracetamol, which are usually present in the form of aqueous suspensions and whose physicochemical stability is deficient due to recrystallization problems.

For the above reasons, oral liquid dosage forms, while beneficial to the patient, are not satisfactory.

In order to overcome the problems with these particular oral formulations, there is now available a solid pharmaceutical dosage form which is reconstituted before administration to the patient. For example, effervescent tablets have the advantages of both the stability of solid dosage form and the convenience of taking liquid dosage form to a certain extent.

However, these dosage forms are not universal and present unique limitations. In the case of effervescent tablet formulations, effervescent tablet formulations contain a large amount of sodium (sodium carbonate or sodium bicarbonate), which makes them unsuitable for elderly people suffering from high blood pressure. Furthermore, the dissolution of the tablet usually takes several minutes, which is usually too long for the patient.

Therefore, there is still a need for a drug delivery system that is easy to administer in the form of liquid medicine, especially for the elderly and children, and does not have the disadvantages of known and commonly used liquid or solid dosage forms.

In order to meet the above conditions, the present invention proposes the use of a drug delivery system comprising a partially soluble matrix containing at least one active ingredient capable of producing a color change when the entire active ingredient is dissolved and absorbed by the patient.

Molecular delivery devices known to us, especially those of the pailles type, comprise dry soluble particles. Drug delivery systems of the pipette type that can absorb particles by suction as described in patent applications WO-03/101.226 and US-5.718.681.

Although these devices can be used for food, they are not suitable for drug delivery.

First, these devices cannot simply visualize the delivery of the drug to the patient.

Second, when a user drinks through a straw, they are physiologically forced to stop inhaling liquid due to the need to inhale again. The liquid in the straw immediately drops by gravity into the glass vessel holding the liquid solution, potentially resulting in loss of ingestible product in the straw. At the same time, it is impossible to accurately determine the portion ingested by the user.

Contents of the invention

The present invention aims to remedy the shortcomings and deficiencies in the prior art.

To this end, the present invention provides an oral drug delivery device in the form of an elongated tubular body comprising means at each end for the intake or discharge of liquid, a one-way valve at one of the two ends , and at least one matrix formed from at least one neutral carrier and a soluble coating that contains an active ingredient and is different in color from the neutral carrier.

Active ingredient is to be understood as any substance having medicinal or therapeutic properties, including probiotics.

Substrate is understood to be any solid substance comprising an excipient and one or more active ingredients which can be dissolved in a liquid. It comprises at least one neutral carrier on which at least one soluble coating is provided. For example, it may exist in the form of flakes, granules, compressed agglomerates, spheres, and the like.

A coating is understood to mean any water-soluble pharmaceutical composition containing at least one active ingredient located on or around a neutral carrier. A coating intended to be swallowed by a patient once dissolved in a liquid, such as a coating, sugar coating or coacervate.

Neutral carrier refers to any water-insoluble or poorly water-soluble carrier that can accommodate one or more layers of coatings and does not contain active ingredients. It consists of materials, preferably inert materials, which do not react with the environment in which the carrier is contained, the active ingredient or the pharmaceutical components. For example, the carrier may be a plastic polymer structure capable of simultaneously holding the coating uniformly and neatly and forming a homogeneous and complete solution immediately upon contact of the coating with a liquid. For example, it can be present in the form of coatings, granules or lumps.

Description of drawings

Now cooperate with accompanying drawing to describe the present invention in detail:

- Figure 1 shows a first embodiment of the device according to the invention, the matrix in granular form,

- Figure 2 shows a cross-sectional view of the device of Figure 1 along the line 2-2,

- figures 3 and 4 show two variants of the matrix in granular form,

- Figure 5 shows a second embodiment of the device according to the invention, the matrix in the form of a mass,

- Figure 6 is a cross-sectional view of the device of Figure 5 along line 6-6,

- Fig. 7 is a third embodiment of the device according to the invention, the matrix is located on the wall of the device,

- Figure 8 is a cross-sectional view of the device of Figure 7 along line 8-8,

- Figure 9 is an enlarged view of the inner wall of the device of Figure 7,

- Figure 10A is a fourth embodiment of the device of the invention,

- Figures 10B to 10F are block diagrams of variants of the device of Figure 10A according to the invention,

- Figure 11 is a cross-sectional view of the device shown in Figure 10A along the line 11-11.

Detailed ways

The present invention relates to an oral drug delivery device 10 in the form of an elongated tubular body comprising means 12, 14 at each end for sucking or expelling a liquid to pass through the volume, at one of the two ends and at least one matrix 18 containing at least one neutral carrier 20 and a soluble coating 22 having a different color from the neutral carrier and containing at least one active ingredient.

The one-way valve 16 may take any form capable of retaining liquid within the device. For example, the one-way valve 16 may be in the form of a ball or a disc.

The one-way valve 16 is preferably spherical, preferably a high-density ball, which has no buoyancy in the aqueous phase liquid.

The device 10 may also include a locking device 34 of the one-way valve 16 . For example, it can be a return element of a connection valve, a stop located inside the tubular body, or a constriction part of the tubular section inside the device 10 .

The device also comprises at least one insert 30 for retaining insoluble substances within the straw. The insert may be foam with pores or grids.

According to another aspect of the invention, the device 10 may have a mouthpiece 35 at the outlet member 12 to allow for easy lip placement by the user during use, enabling precise and instinctive use.

The main body of the device of the present invention may also be a thin tubular body with a tapered end.

The substrate 18 in the device of the present invention at least includes the following:

- neutral carrier 20, and

- A soluble layer 22 having a different color from the neutral carrier and containing at least one active ingredient.

There are several possibilities:

- the carrier 20 is colorless, the coating 22 is colored;

- The carrier 20 is coloured, the outer coating 22 is painted in a different colour.

Preferably, the outer soluble coating 22 is neutral in color, such as yellow-orange, and the carrier 20 is green.

Carrier 20 is neutral. It is an insoluble or slightly soluble carrier in water, on which is provided an optionally pigmented insoluble coating 23 consisting, for example, of shellac or other insoluble polymers such as ethylcellulose.

When the inner carrier 20 is insoluble, it may comprise a polymeric plastic polyethylene or polypropylene plastic and an opacifier.

According to a variant of the invention, said carrier may comprise sugars, polysaccharides, gelled agar, balls of alginate or starch and an opacifying agent.

The carrier may also be formed from a mixture of gelatin and glycerol which is commonly used in capsules in soft capsule form.

When the carrier 20 is dyed, it also contains a colorant.

Outer coating 22 is soluble and contains at least one active ingredient.

According to a preferred embodiment, the outer coating 22 includes:

- diluents, especially selected from the soluble sugar alcohols sorbitol, mannitol, sucrose, lactose or fructose.

-Soluble polymeric binders such as hydrated methylcellulose, hydroxypropylmethylcellulose, methylcellulose and polyvinyl alcohol.

- Povidone, and

- at least one active ingredient.

According to a variant of the invention, the soluble outer coating 22 also contains a co-solvent, for example, a surfactant, such as sodium lauryl sulfate, or a fatty acid ester substance, such as hydrogenated castor oil and its Derivatives, or polysorbate family.

The outer dissolvable coating 22 may also contain sweetening or flavoring agents to improve its taste when ingested by a patient after dissolving in a liquid.

Where outer coating 22 is painted, it may also contain a colorant. Preferably the modifying colorant is a soluble colorant or a pigment fixed to the aluminum paint.

According to a first embodiment of the invention shown in FIG. 1 , device 10 comprises a plurality of matrices 18 .

Each matrix is in the form of particles 24 comprising a neutral inner carrier 20 and at least one soluble outer coating 22 comprising at least one active ingredient and having a different color from the neutral carrier 20 .

The inner carrier 20 may be colorless and the outer coating 22 may be colored, or the inner carrier 20 may be colored and the outer coating 22 may be a different color.

According to a particularly suitable variant as shown in FIG. 4 , the granulate also comprises an insoluble layer 23 between the inner carrier 20 and the outer coating 22 .

Preferably, the particle size is between 0.8 and 4 mm.

The colored particles 24 are prepared either in the form of a mass that is freely placed inside the elongated tubular body or on the wall of the device, so that when liquid flows into the device 10, the drug layer 22 will dissolve.

The particles may also be encapsulated in a porous monolithic matrix, which itself is placed within the elongated tubular body such that the matrix remains insoluble when fluid flows into the device 10 .

Figure 5 shows a second embodiment of the invention in which the matrix 18 is present in the form of a compact 28 comprising an insoluble inner part 20 and a soluble outer part of a different color than the inner part 20 and containing at least one active ingredient.

A compact is to be understood as a powder compact or a homogeneous compact consisting of a continuous polymer.

The compact 28 is preferably a fast disintegrating tablet or vacuum freeze-dried agent.

The compact 28 is prepared and placed inside the thin tube, and when the liquid flows into the device 1, the outer layer 22 containing the active ingredient will dissolve. Its surface area can be increased by surrounding raised portions.

The third embodiment is shown in FIG. 7 . The matrix 18 is an inner coating 32 of tubular cross-section comprising a plurality of layers, which is arranged on the wall 12 . . The neutral carrier 20 is in direct contact with the tubular body or connected with the inner wall of the tubular body. It is covered by a soluble coating 22 containing at least one active ingredient, which is in contact with the liquid flowing into the device 10 and which exhibits a different color from the neutral carrier 20 .

According to a fourth embodiment, which is easy to implement, as shown in FIG. 10A , the matrix 18 can also form the one-way valve 16 or be placed on the one-way valve 16 . The tubular portion of the device 10 tapers towards the end 14 and also has an upper locking means 34 of the ball 16 .

Preferably, the one-way valve 16 is a high-density ball and includes an insoluble neutral carrier 20 and an outer soluble coating 22 that is different in color from the neutral carrier and contains at least one active ingredient.

In this case, since the tubular portion tapers towards one end, once the outer coating 22 dissolves, the reduced diameter ball will always function as a valve.

Advantageously, the device of the present invention allows accurate and reproducible dosing of drugs in readily absorbable liquid form.

When the patient inhales the liquid through the device 10 of the present invention like water or milk, the outer coating 22 containing the medicinal ingredients dissolves and is drunk by the patient together with the liquid. The insoluble neutral carrier 20 remains in the container.

Advantageously, because the neutral carrier 20 is a different color than the outer coating 22, the container of the present invention will change color when all active ingredients are dissolved and inhaled by the patient. We can observe the administered drug being ingested. This indication ensures that the required dose is ingested while preventing the patient from ingesting too much fluid.

In addition, the presence of the one-way valve 16 prevents a portion of the dissolved active ingredient from flowing back into the glass container containing the solution. So we can precisely control the amount of active ingredient that the patient ingests.

Figures 10B to 10F are different steps in the use of an embodiment of the invention, in particular the illustrated inventive device. In this embodiment, the substrate 18 is positioned over the spherical one-way valve 16 .

First, the user places the device 10 in a glass vessel filled with liquid and inhales it through the mouthpiece 35 . The negative pressure created in the tube lifts the ball 16, opening the inlet 14 and causing the liquid to rise through the device. The outer coating 22 placed on the ball dissolves and the active ingredient dissolved in the liquid is then inhaled by the patient. If the patient stops inhaling, the ball 16 falls again, preventing the dissolved and undrinked active ingredient from flowing back into the glass. The patient can re-inhale until a color change occurs, indicating that all the active ingredient has been ingested.

The device of the invention makes it easy for patients to administer medicines, especially for the elderly and children, the medicines can be controlled.

For example, if the outer soluble coating 22 is a neutral orange-yellow and the neutral carrier 20 is green, when the product is used, the outer orange-yellow coating containing the active ingredient gradually dissolves and the underlying layer appears green. When the matrix 18, ie the device, turns completely green, all the active ingredients with medicinal properties have been dissolved and absorbed by the patient.

The present invention will now be further described by exemplifying the manufacture of the first embodiment of the present invention.

Example 1: Yellow/Green Discolored Particles

In this example, the device 10 of the present invention comprises a granulated substrate 18 , each granule comprising a green insoluble neutral carrier 20 , a colorless insoluble intermediate layer 23 , and a yellow outer coating 22 .

The composition of the different coatings is shown in the table below:

Element quantity Internal neutral carrier (green and insoluble in water) 2mm neutral particle coated green solution OPADRY 2Green 1g0.034g Intermediate layer (colorless and insoluble in water) Ethyl cellulose 0.3g Coating (yellow and soluble in water) Acetaminophen Sucrose Povidone Talc Turmeric E100 Cranberry Flavor 0.150g1.600g0.045g0.520g0.060g0.050g

The device can be prepared according to the following procedure:

Step 1: Preparation of green neutral carrier

(羟丙甲纤维素、滑石、葡聚糖、麦芽糖糊精、蓝色FD&C漆、喹啉黄漆、二氧化钛、甘油三酯)Add 500g of purified water to a 1-liter stainless steel tank, then stir in 75g of the prepared coated green dye OPADRY II

(Hypromellose, Talc, Dextran, Maltodextrin, Blue FD&C Lacquer, Quinoline Yellow Lacquer, Titanium Dioxide, Triglycerides)

Stir with the aid of a spiral deflocculating stirrer until a thick green homogeneous suspension is formed.

Step 2: Deposition of the green neutral carrier

Add 1000 g of neutral sucrose granules with a diameter of 2 mm in the fluidized granulator.

The air flow is adjusted to suspend the particles, and the incoming air is +60°C +/- 10°C.

The green coating solution prepared in step 1 was started to be sprayed and then deposited to obtain particles with a mass of 1.230 kg.

Step 3: Preparation of neutral immiscible liquid

的形式加入)，搅拌至形成匀质制剂。Add 600ml of pure water into a 1000ml volume stainless steel tank, and stir in 400g of ethyl cellulose in the form of water dispersion (equivalent to 100g of dry weight, expressed as Surealease

form), and stir until a homogeneous preparation is formed.

Step 4: Deposition of a colorless insoluble film:

The air flow was adjusted to suspend the granules in a fluidized granulator containing green granules (1.230 kg) and the incoming air was +60°C +/- 10°C.

Spraying of a colorless paint solution insoluble in the film prepared in step 3 was started and the solution was subsequently deposited to obtain granules with a mass of 1.330 kg.

Step 5: Preparation of colored solution containing medicinal ingredients

Add 258ml of pure water into a stainless steel tank with a capacity of 1 liter, and stir in the following different ingredients in stages:

Acetaminophen 37.50g

Sucrose 400.00g

Povidone 11.25g

Talc 129.00g

Curcumin E100 14.70g

Cranberry Spice 12.54g

Stir until a homogeneous formulation is formed. The formulation was filtered through a filter with a mesh size of 0.1 mm to ensure complete dispersion of suspended matter.

Step 6: Deposition of colored solution containing medicinal ingredients

The airflow is adjusted to suspend the granules in the fluidized granulator containing the green granules coated with insulating varnish, and the incoming air is +60°C +/- 10°C.

The prepared solution is deposited to obtain colored medicinal ingredient-containing particles.

Step 7: Filling of the Straw

A one-way valve 16 is added at the other end of the tubular body to fill the suction pipe with the colored granules that have reached a sufficient dose of medicine.

Close the suction tube with the suction nozzle 35.

Example 2: Red/Green Changed Particles

In this example, the device 10 according to the invention comprises a matrix 18 in the form of granules, each granule comprising a green insoluble neutral carrier 20 , a colorless insoluble intermediate layer 23 , and a red outer coating 22 .

The composition of the different coatings is shown in the table below:

Element quantity Internal neutral carrier (green and insoluble in water) 2mm neutral particle coated green solution OPADRY 2Green 1g0.034g Intermediate layer (colorless and insoluble in water) Ethyl cellulose 0.3g Coating (red and soluble in water) Ibuprofen Sucrose Povidone Talc Aspartame E120 Strawberry Flavor 0.100g1.600g0.045g0.520g0.050g0.060g0.050g

Example 3: Red/White Discolored Particles

In this example, the device 10 according to the invention comprises a matrix 18 in the form of granules, each granule comprising a colorless insoluble neutral carrier 20 and a red outer coating 22 .

The composition of the different coatings is shown in the table below:

Element quantity Internal neutral carrier (colorless and insoluble in water) Ethyl cellulose titanium dioxide 0.3g0.05g Coating (red and soluble in water) Ibuprofen Sucrose Povidone Talc Aspartame E120 Strawberry Flavor 0.100g1.600g0.045g0.520g0.050g0.060g0.050g

Of course, the invention is not limited to the above-mentioned examples, but can include all variants.

Claims (18)

1. the oral drug administration device of elongate body form (10), comprise and be positioned at sucking or the parts (12,14) of drain of each end, it is characterized in that, its end in both ends has check valve (16), and at least a substrate (18), this substrate comprises the insoluble carrier of at least a neutrality (20) and solvable coating (22), this coating comprises at least a active component and has the color different from neutral carrier, and this device comprises that also at least one is used for insoluble matter is kept at insert in the suction pipe.

2. oral drug administration device according to claim 1 (10) is characterized in that, described solvable coating (22) is coloured.

3. oral drug administration device according to claim 1 (10) is characterized in that, the insoluble carrier of described neutrality (20) is coloured.

4. oral drug administration device according to claim 1 (10) is characterized in that, the insoluble carrier of described neutrality (20) comprises polyethylene or polypropylene plastics polymer, and opacifier, and optional coloring agent.

5. oral drug administration device according to claim 1 (10) is characterized in that, the insoluble carrier of described neutrality (20) comprises the agar of sugar, gelation or the ball of starch, and opacifier, and optional coloring agent.

6. oral drug administration device according to claim 5 (10) is characterized in that, described sugar is polysaccharide.

7. each described oral drug administration device (10) in 5 according to claim 1 is characterized in that the insoluble carrier of described neutrality (20) comprises the mixture of gelatin, glycerol and optional coloring agent.

8. each described oral drug administration device (10) in 5 according to claim 1 is characterized in that described solvable coating (22) contains at least a active component, diluent, binding agent and optional coloring agent.

9. oral drug administration device according to claim 8 (10) is characterized in that, described diluent is neutral filler.

10. oral drug administration device according to claim 8 (10) is characterized in that, described binding agent is polyvidone.

11. each described oral drug administration device (10) in 5 is characterized in that described solvable coating (22) contains at least a active component, cosolvent according to claim 1, and optional coloring agent.

12. each described oral drug administration device (10) in 5 is characterized in that described solvable coating (22) contains a kind of coloring agent of alumin(i)um paint form according to claim 1.

13. each described oral drug administration device (10) in 5 according to claim 1, it is characterized in that, this device contains the substrate (18) of a plurality of granules (24) form, each granule (24) comprises neutral insoluble carrier (20) and the outer solvable coating (22) of one deck at least, and the solvable coating of described skin contains at least a active component and insoluble carrier from described neutrality (20) color is different.

14. oral drug administration device according to claim 13 (10) is characterized in that described particle size is between 0.8 to 4mm.

15. each described oral drug administration device (10) in 5 according to claim 1, it is characterized in that, described substrate (18) exists with compact heap (28) form, this compact heap by the insoluble interior section of neutrality (30) and at least the soluble skin of one deck (32) form, described skin (32) contains at least a active component and insoluble interior section from described neutrality (30) has different colors.

16. each described oral drug administration device (10) in 5 is characterized in that described check valve (16) is ball according to claim 1.

17. each described oral drug administration device (10) in 5 is characterized in that it comprises the locking device (34) of check valve (16) according to claim 1.

18. each described oral drug administration device (10) in 5 is characterized in that according to claim 1, this device is elongate body, and tubular portion dwindles gradually towards the end in the two ends.

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